Impact of visit-to-visit variability in blood pressure on coronary plaque as assessed by integrated backscatter intravascular ultrasound.

INTRODUCTION: Visit-to-visit variability (VVV) in blood pressure (BP) has been reported to be a strong predictor of cardiovascular disease. However, the association between VVV in BP and coronary plaque composition has not been fully elucidated. METHODS: One hundred-two consecutive patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) using integrated backscatter (IB) intravascular ultrasound (IVUS), and who had at least six clinic visits a year before PCI were included. We measured systolic and diastolic BP (SBP and DBP) at each visit and determined VVV in BP expressed as the standard deviation of the average BP. Grayscale and IB IVUS examinations were performed for the culprit lesion of a coronary artery just before PCI. RESULTS: There were no significant associations between the average SBP or DBP and various IVUS parameters. However, VVV in SBP was positively correlated with both the percentage (%) of atheroma volume (ß = 0.23, p = .02) and % lipid volume (ß = 0.53, p < .0001). VVV in DBP was positively correlated with % lipid volume (ß = 0.24, p = .01), while there was no significant correlation between VVV in DBP and % atheroma volume. A  multivariable linear regression analysis showed that VVV in SBP was independently associated with % atheroma volume (p = .04) and % lipid volume (p < .001). CONCLUSIONS: Larger VVV in SBP was significantly associated with an increased plaque burden and lipid composition at the culprit lesion of a coronary artery in CAD patients. The improvement of VVV in SBP may contribute to the regression and stabilization of coronary plaques.

Influence of chronic kidney disease on coronary plaque components in coronary artery disease patients with both diabetes mellitus and hypertension.

Chronic kidney disease (CKD) is well known to be associated with an increased incidence of coronary artery disease (CAD). Diabetes mellitus (DM) and hypertension (HTN), both of which are traditional risk factors for CAD, are the two most common causes of CKD. However, the influence of CKD on coronary atherosclerosis in CAD patients who have both DM and HTN remains uncertain. In these patients, we examined the relationship between CKD and coronary plaque using integrated backscatter intravascular ultrasound (IB IVUS). Two hundred two CAD patients with both DM and HTN who underwent percutaneous coronary intervention using IB IVUS were included. The patients were divided into two groups: CKD group (n = 106) and non-CKD group (n = 96). Gray-scale and IB IVUS examinations were conducted for the non-culprit segment of a coronary artery. As a result, although there was no significant difference in the percentage of plaque volume, the percentage of lipid volume was significantly higher in the CKD group than in the non-CKD group [median (IQR): 56.7% (45.4-67.0%) vs. 52.0% (38.3-60.2%), p = 0.03]. In all of the patients, estimated glomerular filtration rate levels were negatively correlated with the percentage of lipid volume (r = - 0.15, p = 0.03) and positively correlated with the percentage of fibrosis volume (r = 0.15, p = 0.04). A multivariate regression analysis showed that CKD was an independent predictor associated with the increased lipid volume (ß = 0.15, p = 0.047) and decreased fibrosis volume (ß = - 0.16, p = 0.03) in coronary plaques. In conclusion, among CAD patients who had both DM and HTN, CKD was associated with lipid-rich coronary plaques. CKD may contribute to the vulnerability of coronary plaque in these very high-risk patients.

Impact of the triglyceride level on coronary plaque components in female patients with coronary artery disease treated with statins.

Several studies have reported that elevated triglyceride (TG) levels may be more strongly associated with an increased risk of coronary artery disease (CAD) in females than in males. We examined gender differences in the relationship between TG levels and coronary atherosclerosis using integrated backscatter intravascular ultrasound (IB IVUS) in CAD patients treated with statins. Three hundred seventy-eight CAD patients (105 females and 273 males) who underwent percutaneous coronary intervention using IB IVUS, and who were already receiving statin treatment, were included. Gray-scale and IB IVUS examinations were performed for the non-culprit segment of a coronary artery and fasting serum TG concentrations were measured. We found that TG levels were significantly correlated with increased lipid (r = 0.40, p < 0.001) and decreased fibrous (r = - 0.37, p < 0.001) plaque components in females, but not in males. Low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were not related to either the gray-scale or IB IVUS parameters in both genders. After adjustment for conventional coronary risk factors by a multivariate stepwise regression analysis, higher TG levels in females were independently associated with increased lipid (ß = 0.31, p< 0.001) contents in coronary plaques. In conclusion, among CAD patients treated with statins, TG levels were associated with lipid-rich coronary plaques in females, but not in males. TG levels may be more important indicators of residual risk after statin treatment in females than in males.

Retroperitoneal liposarcoma excreting insulin-like growth factor 2 that induced severe hypoglycemia.

Insulin-like growth factor 2 is overexpressed in various cancers, and is associated with a poor prognosis. Also, it is known that insulin-like growth factor 2 is an etiology of non-islet cell tumor hypoglycemia. In this report, we describe a case of unexpected hypoglycemia caused by a dedifferentiated liposarcoma producing insulin-like growth factor 2. A large mass in the retroperitoneum was detected in a 61-year-old man who complained of appetite loss. Despite having no history of diabetes mellitus, hypoglycemia suddenly occurred after admission, but oral glucose therapy was ineffective. After total parenteral nutrition, tumor resection was attempted, but failed as a result of rigid adhesion to the surrounding organs. The patient died of the disease 21 days after surgery. Pathological diagnosis at autopsy revealed dedifferentiated liposarcoma, and immunohistochemical staining showed that the tumor excreted insulin-like growth factor 2. The possibility of an insulin-like growth factor 2-producing tumor should be taken into consideration when we encounter a patient with spontaneous hypoglycemia resistant to glucose substitution therapy.

Antimicrobial prophylaxis to prevent perioperative infection in urological surgery: a multicenter study.

We prospectively investigated the rates of incidence of surgical site infection (SSI), urinary tract infection (UTI), and remote infection (RI) in 4,677 patients who underwent urological surgery from January to December 2010, including 2,507 endourological cases, 1,276 clean cases, 807 clean-contaminated cases, and 87 contaminated cases involving bowel segments. A single dose of antimicrobial prophylaxis (AMP) was administered in the endourological, clean, and clean-contaminated surgery cases, except for patients who underwent transurethral resection of the prostate (TURP) or percutaneous nephrolithotripsy (PNL). AMP was administered within 72 h in TURP and PNL, and AMP was administered within 48 h in contaminated surgery cases. In cases of endourological surgery, UTI was observed in 4% and RI in 0%, and SSI, UTI, and RI were seen in 1%, 1%, and 1%, respectively, of clean surgery cases, in 3%, 3%, and 2%, respectively, of clean-contaminated surgery cases, and in 17%, 30%, and 10%, respectively, of contaminated surgery cases. In multivariate analysis of the risk factors for infection, operative time was a significant risk factor for UTI in endourological surgery, and American Society of Anesthesiologists score and operative time were significant risk factors for RI in clean surgery. No significant risk factor was found in analyses of clean-contaminated and contaminated surgery cases. A single-dose AMP regimen was shown to be effective and feasible for prevention of perioperative infection in urological surgery.

Adult influenza epidemic is associated with out-of-hospital cardiac arrest: From the All-Japan Utstein Registry, a prospective, nationwide, population-based, observational registry.

ABSTRACT: It has been reported that influenza infection is associated with out-of-hospital cardiac arrest of cardiac origin (OHCA-CA). However, the association between OHCA-CA and influenza epidemics in adults has not been well investigated.We analyzed data from the All-Japan Utstein Registry, a prospective, nationwide, population-based, observational study, regarding OHCA-CA cases and the Infectious Diseases Weekly Report for influenza cases: 17,710 OHCA-CA cases and 764,808 influenza cases were recorded between 2005 and 2015 in Fukuoka, Japan. The weekly average number of OHCA-CA cases was positively associated with the number of patients with influenza infection (r = 0.70, P < .0001). To eliminate the effects of season and age, we investigated only adults in winter. The weekly number of OHCA-CA cases was positively associated with the number of patients with influenza infection in weeks when there was a high frequency of influenza infection in adults (r = 0.36, P = .006), but not in weeks with a medium (r = 0.26, P = .05) or low frequency of influenza infection (r = 0.003, P = 1.0). In weeks during which there was a high frequency of influenza infection, the weekly number of OHCA-CA cases was positively associated with the number of influenza infections in males (r = 0.37, P = .006), but not females (r = 0.18, P = .2).The number of OHCA-CA cases was positively associated with the number of influenza infections in adult males during weeks in which there was a high frequency of influenza infections. To help prevent OHCA-CA in males, it might be beneficial to announce influenza epidemics specifically in adults, in addition to all ages.

Effect of a phytotherapeutic agent, Eviprostat®, on prostatic and urinary cytokines/chemokines in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation in the prostate has recently been recognized as an important component of the symptom progression of benign prostatic hyperplasia. The objective of this study was to evaluate a range of cytokines/chemokines in prostate tissue and urine to identify markers of prostate inflammation in a prostatitis model and to investigate the effect of a phytotherapeutic agent, Eviprostat®, on these markers. METHODS: Ten-month-old male Wistar rats were divided into four groups. Nonbacterial prostatitis (NBP) was experimentally induced in groups 2-4 by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. Control rats were fed a standard diet, while animals in the Eviprostat groups were fed a diet containing 0.05 or 0.1% Eviprostat for 30 days. The levels of cytokines/chemokines in prostate tissue on the 31st day and in urine collected the day before castration and the day before removal of the prostate were determined. RESULTS: Experimentally induced NBP increased the prostatic levels of the cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The levels of the chemokines CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage inflammatory protein-1α (MIP-1α), CXCL1/CINC-1, CXCL3/CINC-2, and CXCL5/LIX were elevated in both prostate and urine. Eviprostat significantly suppressed the increases in prostate IL-1ß, TNF-α and CCL3/MIP-1α and prostatic and urinary CCL2/MCP-1 and CXCL1/CINC-1. CONCLUSIONS: Chemokines, including CCL2/MCP-1 and CXCL1/CINC-1, were elevated in the prostate and urine of NBP rats, and Eviprostat potently suppressed the increases in CCL2/MCP-1 and CXCL1/CINC-1. These chemokines are therefore candidate diagnostic biomarkers for nonbacterial chronic prostatic inflammation.

Acquired cystic disease-associated renal cell carcinoma: an immunohistochemical and fluorescence in situ hybridization study.

Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has been recently identified. However, there are only a few genetic studies to date. In this article, we performed an immunohistochemical and fluorescence in situ hybridization (FISH) study for six cases including one case with sarcomatoid change. As a result, we observed frequent immunohistochemical expression of AMACR. FISH of chromosome 3 showed trisomy for three cases, monosomy for two cases, and disomy for one case. Additionally, FISH of chromosome 16 showed trisomy for three cases, monosomy for two cases, and both trisomy and monosomy for one case. Furthermore, both the carcinomatous area and the sarcomatoid area of one ACD-associated RCC with sarcomatoid change revealed monosomy of chromosomes 3, 9, and 16 but showed disomy of chromosome 14. In conclusion, the numerical abnormalities of chromosomes 3 and 16, irrespective of gain or loss, may be characteristic of ACD-associated RCC.

[A case with hepatitis and interstitial pneumonitis caused by intravesical bacillus Calmette-Guérin (BCG) instillation].

A 49-year man, with past history of right total nephroureterectomy due to urothelial carcinoma of the right renal pelvis in September 2006 and left partial ureterectomy due to contralateral ureteral recurrence in October 2007, underwent TUR-BT due to superficial high-grade recurrent bladder cancer. After TUR-Bt, he was treated with intravesical Bacillus Calmette-Guérin (BCG) instillation at weekly intervals. Just after 5th instillation, he suffered a continuous high fever up to 38 degrees C and complained of general fatigue. Chest CT showed diffuse micronodular shadows in both lungs, and serum liver enzyme was markedly elevated. All cultures from his sputum and urine were negative for mycobacterium tuberculosis. TB-PCR test and quantiferon were also negative. These findings together with no improvement of the symptoms with anti-tuberculous treatment finally made us to judge that this was due to a hypersensitivity reaction to BCG. Soon after pulse steroid therapy, body temperature was normalized and the abnormal findings of the lung and liver disappeared.

Renal cell carcinoma in patients with end-stage renal disease: relationship between histological type and duration of dialysis.

OBJECTIVE: To evaluate the clinical outcomes and histological types of renal cell carcinoma (RCC) arising in patients with end-stage renal disease (ESRD), and to analyse the relationship of histopathological features with the duration of dialysis. PATIENTS AND METHODS: Clinical characteristics and outcomes of 34 patients who had a radical nephrectomy for RCC arising in ESRD between November 1994 and June 2008 were investigated. Archive paraffin-embedded tissue specimens obtained from 27 patients were histochemically and immunohistochemically analysed to determine the histopathological type. RESULTS: There was one death from cancer and one patient with local progression within a median observation period of 29.5 months. Acquired cystic disease (ACD)-associated RCC, clear cell-papillary RCC, mucinous tubular and spindle-cell carcinoma, and Xp11.2 translocation/TFE3 gene fusion were identified in eight, two, three and one patient, respectively. Conventional clear-cell RCC was the predominant histological type (nine of 15) in patients with a duration of dialysis of <10 years, while ACD-associated RCC was predominant (seven of 12) in those with dialysis for > or =10 years. Sarcomatoid foci were identified in three patients with dialysis for > or =10 years. Papillary adenoma was microscopically identified as a satellite tumour in 10 patients. CONCLUSION: The spectrum of histological types of RCCs arising in ESRD is distinct from that of sporadic RCCs. Patients with a longer duration of dialysis should have particular attention for progression and metastasis. Immunohistochemical profiling is efficient in the histological classification of RCCs arising in ESRD, although knowledge about genetic changes remains to be accumulated.

Hereditary Antithrombin Deficiency Presenting with Deep Venous Thrombosis During the Second Pregnancy.

A 37-year-old woman developed deep venous thrombosis (DVT) of the left lower extremity at 8 weeks of gestation during her second pregnancy. There was no personal or family history of thrombosis. She received intravenous heparin, but heparin resistance was noted. The plasma antithrombin activity decreased to 45% in the acute phase, and it remained low postpartum. Her mother also had low plasma antithrombin activity (46%), and genetic testing revealed a heterozygous SERPINC1 mutation. Even without a family history of thrombosis, we should suspect hereditary antithrombin deficiency in patients with initial DVT and perform thorough investigation.

Impact of von Willebrand factor on coronary plaque burden in coronary artery disease patients treated with statins.

High von Willebrand factor (VWF) levels have been reported to be associated with an increased risk of cardiovascular events. However, the relationship between VWF levels and coronary atherosclerosis in patients with coronary artery disease (CAD) who have already received stain treatment is still unclear. We examined the association between VWF levels and coronary plaque as assessed by intravascular ultrasound (IVUS) in CAD patients treated with statins. Ninety-one CAD patients who underwent percutaneous coronary intervention under IVUS guidance, and who were already receiving statin treatment based on Japanese guidelines, were included. An IVUS examination was performed for the culprit lesion, and plasma VWF antigen levels were measured using enzyme-linked immuno sorbent assay. In all of the patients, the low-density lipoprotein cholesterol levels just before the IVUS examination were low (86 ± 26 mg/dL). The VWF levels were positively correlated with the plaque burden expressed as percent atheroma volume (PAV) (r = 0.39, P = .001), while there was no significant association between VWF and plaque composition. Multivariate stepwise regression analysis showed that higher VWF levels were independently associated with increased PAV (ß=0.26, P = .01). In CAD patients who had already been treated with statins, higher VWF levels were associated with a higher coronary plaque burden, suggesting that a high VWF level may be a marker of the residual cardiovascular risk after statin treatment.

Short-term effects of TNP-470 in combination with cisplatin in the rat model of bladder cancer.

PURPOSE: To investigate the short-term effects of TNP-470 in combination with cisplatin in a rat model of bladder cancer. MATERIALS AND METHODS: Following treatment of TNP-470 with or without cisplatin for 7 days, the states of angiogenesis, apoptosis and cell proliferation were evaluated in rat bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. RESULTS: In comparison with untreated tumors, we noted a significantly decreased microvessel density (MVD) in the rat bladder cancer treated by TNP-470, and a significantly increased apoptotic index (AI) when treated by cisplatin. In TNP-470 plus cisplatin-treated tumors, both significantly decreased MVD and increased AI were observed in non-invasive and invasive rat bladder cancers in addition to a significantly decreased proliferation index (PI) in invasive cancer. CONCLUSION: The combination therapy of TNP-470 with cisplatin may act through both the inhibition of angiogenesis and induction of apoptosis, and invasive tumor cells may be much more sensitive to this combined therapy in rat bladder cancer.

Micturitional disturbance due to labial adhesion as a cause of vaginal implantation of bladder urothelial carcinoma.

Vaginal implantation of urinary tract urothelial carcinoma is a rare finding, with few cases reported in the literature. This is the first reported case of vaginal implantation of bladder urothelial carcinoma thought to be due to micturitional disturbances secondary to labial adhesion. The authors propose that implantation via pooled urine in the vagina may have occurred, and suggest that labial adhesion be treated in patients with urinary tract urothelial carcinoma, even if asymptomatic.

Ten cases of congenital urethral stricture in childhood with enuresis.

BACKGROUND: To report short-term clinical outcomes of endoscopic correction of congenital urethral stricture in 10 boys who suffer from enuresis resistant to conservative therapy. METHODS: Fifteen boys ranging between 5 and 15 years old consulted our clinics for nocturnal and diurnal enuresis which had not been improved by medication and behavioral therapy. Among them, voiding cystography revealed bulbar narrowing (Cobb's Collar) in 10 cases and vesico-ureteral reflux was found in four cases (seven ureters). Endoscopically, this lesion was recognized as a ring-form stenosis just distal to the urethral sphincter. It was incised with infantile urethrotome. RESULTS: Vesico-ureteral reflux was resolved in four ureters and improved in one. In all cases, daytime enuresis resolved dramatically and night enuresis became controllable. CONCLUSIONS: Boys who suffer from diurnal enuresis should immediately be explored for the existence of congenital urethral stenosis. Early resolution may bring about better urinary behavior.

Angiogenesis in renal cell carcinoma: Evaluation of microvessel density, vascular endothelial growth factor and matrix metalloproteinases.

BACKGROUND: Angiogenesis, the growth of new blood vessels, has a critical role in tumor growth and metastasis. The purpose of this study was to investigate the involvement of angiogenesis and angiogenic factors in the pathogenesis of renal cell carcinoma (RCC). METHODS: Formalin-fixed and paraffin-embedded tissue blocks from 70 patients with RCC were studied. The situations of tumor angiogenesis were evaluated by assessing microvessel density (MVD) through CD31 immunostaining. The expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) was detected immunohistochemically. RESULTS: The value of MVD ranged from 12.0 to 93.0 with a median of 39.91 in RCC. Of the 70 RCCs, the expression of VEGF was detected in 52 (74.3%), MMP-2 in 29 (41.4%) and MMP-9 in 19 (27.1%) cases. Statistical analysis revealed significant associations of the tumor stage with MVD, and the expression of VEGF and MMP-2 in RCC. Additionally, MVD was closely related to the expression of VEGF but was not related to the expression of MMP-2 and MMP-9 in RCC. CONCLUSION: The degree of angiogenesis may be closely related to the tumor progression of RCC. The expression of VEGF may be responsible for angiogenesis in RCC, and both VEGF and MMP-2 expression may function as tumor associated angiogenic factors in RCC.

Transitional cell carcinoma of the ureteral stump eight years after nephrectomy for benign disease.

A case of primary carcinoma of the ureteral stump is reported. A 68-year-old man presented with asymptomatic gross hematuria. He had undergone a right nephrectomy for a benign disease previously. Cystoscopy and left ureteroscopy showed no abnormalities. A computed tomography showed a solid mass on the region of the right ureteral stump. He underwent a right ureterectomy and bladder cuff resection. A pathological examination showed transitional cell carcinoma.

Determination of percent area density of epithelial and stromal components in development of prostatic hyperplasia in spontaneously hypertensive rats.

OBJECTIVES: To determine the percent area density of epithelial and stromal components in the development of prostatic hyperplasia in spontaneously hypertensive (SH) rats. METHODS: The ventral lobes of prostates obtained from male SH rats and their normotensive counterparts, Wistar Kyoto (WKY) rats, were examined histopathologically at 15, 29, 40, and 54 weeks of age (5 SH and WKY rats each at each age group). The degree of prostatic hyperplasia was evaluated with a score-chart protocol, histoscore. The percent area density of epithelium and stroma of the ventral prostate were determined using a computerized image analysis system. RESULTS: Definite lesions of hyperplastic changes were demonstrated in the ventral prostate of SH rats from 15 to 54 weeks. In comparison with WKY rats, SH rats showed a significantly increased degree of prostatic hyperplasia as reflected by the histoscore values. Furthermore, the histoscore of the ventral prostate of SH rats increased with age (from 21.7 +/- 0.7 at 15 weeks to 26.1 +/- 0.4 at 54 weeks). The percent area density of epithelium and stroma were significantly increased in SH rats, and the ratio of stroma to epithelium ranged from 1:2.94 to 1:3.50 in SH rats but was maintained at 1:1.15 to 1:1.19 in WKY rats during the observation period. CONCLUSIONS: The hyperplastic changes of the ventral prostate may develop with advancing age in SH rats. The development of prostatic hyperplasia may result from both epithelial and stromal proliferation and may be predominantly expressed as a glandular type in SH rats.